Synlett, Table of Contents Synlett 2015; 26(11): 1549-1552DOI: 10.1055/s-0034-1380713 letter © Georg Thieme Verlag Stuttgart · New York Palladium-Catalyzed Approach to Malasseziazole A and First Total Synthesis of Malasseziazole C Ute Kober Department Chemie, Technische Universität Dresden, Bergstr. 66, 01069 Dresden, Germany Email: hans-joachim.knoelker@tu-dresden.de , Hans-Joachim Knölker* Department Chemie, Technische Universität Dresden, Bergstr. 66, 01069 Dresden, Germany Email: hans-joachim.knoelker@tu-dresden.de › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Dedicated to Professor K. Peter C. Vollhardt on the occasion of his 69th birthday Abstract We describe a convergent route to 5,11-dihydroindolo[3,2-b]carbazoles using a twofold oxidative cyclization as key step. The method has been applied to the synthesis of a precursor for malasseziazole A and to the first total synthesis of malasseziazole C. Key words Key wordsalkaloids - catalysis - cyclization - indolocarbazoles - natural products - palladium Full Text References References and Notes 1 Gupta AK, Bluhm R, Summerbell R. J. Eur. Acad. Dermatol. Venerol. 2002; 16: 19 2 Irlinger B, Bartsch A, Krämer H.-J, Mayser P, Steglich W. Helv. Chim. Acta 2005; 88: 1472 3 Zuther K, Mayser P, Hettwer U, Wu W, Spiteller P, Kindler BL. J, Karlovsky P, Basse CW, Schirawsky J. Mol. Microbiol. 2008; 68: 152 4a Chakraborty DP, Roy S In Progress in the Chemistry of Organic Natural Products . Vol. 57. Herz W, Grisebach H, Kirby GW, Steglich W, Tamm C. Springer; Wien: 1991: 71 4b Chakraborty DP In The Alkaloids . Vol. 44. Cordell GA. Academic Press; New York: 1993: 257 5a Knölker H.-J, Reddy KR. Chem. Rev. 2002; 102: 4303 5b Knölker H.-J, Reddy KR In The Alkaloids . Vol. 65. Cordell GA. Academic Press; Amsterdam: 2008: 1 5c Schmidt AW, Reddy KR, Knölker H.-J. Chem. Rev. 2012; 112: 3193 For reviews on indolocarbazoles, see: 6a Bergman J, Janosik T, Wahlström N. Adv. Heterocycl. Chem. 2001; 80: 1 6b Sánchez C, Méndez C, Salas JA. Nat. Prod. Rep. 2006; 23: 1007 6c Janosik T, Wahlström N, Bergman J. Tetrahedron 2008; 64: 9159 7a Tholander J, Bergman J. Tetrahedron Lett. 1998; 39: 1619 7b Tholander J, Bergman J. Tetrahedron 1999; 55: 6243 8 Tholander J, Bergman J. Tetrahedron 1999; 55: 12577 9a Yudina LN, Bergman J. Tetrahedron 2003; 59: 1265 9b Wahlström N, Romero I, Bergman J. Eur. J. Org. Chem. 2004; 2593 9c Van Snick S, Dehaen W. Org. Biomol. Chem. 2012; 10: 79 10a Rannug A, Rannug U, Rosenkranz HS, Winqvist L, Westerholm R, Agurell E, Grafström A.-K. J. Biol. Chem. 1987; 262: 15422 10b Rannug U, Rannug A, Sjöberg U, Li H, Westerholm R, Bergman J. Chem. Biol. (Oxford, U.K.) 1995; 2: 841 10c Öberg M, Bergander L, Håkansson H, Rannug U, Rannug A. Toxicol. Sci. 2005; 85: 935 11 Forke R, Jäger A, Knölker H.-J. Org. Biomol. Chem. 2008; 6: 2481 12 Part 124 of Transition Metals in Organic Synthesis; for Part 123, see: Hesse R, Schmidt AW, Knölker H.-J. Tetrahedron 2015; 71: in press ; doi: 10.1016/j.tet.2015.03.064 For reviews, see: 13a Knölker H.-J. Curr. Org. Synth. 2004; 309 13b Knölker H.-J. Chem. Lett. 2009; 38: 8 13c Bauer I, Knölker H.-J. Top. Curr. Chem. 2012; 309: 203 For recent applications, see: 14a Gruner KK, Knölker H.-J. Org. Biomol. Chem. 2008; 6: 3902 14b Börger C, Krahl MP, Gruner M, Kataeva O, Knölker H.-J. Org. Biomol. Chem. 2012; 10: 5189 14c Hesse R, Gruner KK, Kataeva O, Schmidt AW, Knölker H.-J. Chem. Eur. J. 2013; 19: 14098 14d Kumar VP, Gruner KK, Kataeva O, Knölker H.-J. Angew. Chem. Int. Ed. 2013; 52: 11073 14e Hesse R, Jäger A, Knölker H.-J. Org. Biomol. Chem. 2014; 12: 3866 14f Hesse R, Krahl MP, Jäger A, Kataeva O, Schmidt AW, Knölker H.-J. Eur. J. Org. Chem. 2014; 4014 14g Gassner C, Hesse R, Schmidt AW, Knölker H.-J. Org. Biomol. Chem. 2014; 12: 6490 15a Knölker H.-J, Reddy KR. Tetrahedron Lett. 1998; 39: 4007 15b Knölker H.-J, Reddy KR. Tetrahedron 2000; 56: 4733 16 Zhuang J, Wang C, Xie F, Zhang W. Tetrahedron 2009; 65: 9797 17a Charles MD, Schulz P, Buchwald SL. Org. Lett. 2005; 7: 3965 17b Surry DS, Buchwald SL. Angew. Chem. Int. Ed. 2008; 47: 6338 18 2′,5′-Bis(phenylamino)acetophenone (5) Orange oil. IR (ATR): ν = 3380, 3276, 3034, 2921, 2851, 1641, 1619, 1595, 1575, 1512, 1492, 1465, 1420, 1398, 1360, 1306, 1245, 1204, 1076, 1025, 994, 957, 933, 874, 814, 743, 692, 664 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 2.57 (s, 3 H), 6.74 (t, J = 7.3 Hz, 1 H), 6.94–7.03 (m, 3 H), 7.17–7.20 (m, 4 H), 7.25–7.33 (m, 4 H), 7.62 (d, J = 1.9 Hz, 1 H), 7.98 (br s, 1 H), 9.88 (br s, 1 H). 13C NMR and DEPT (125 MHz, DMSO-d 6): δ = 28.53 (CH3), 114.91 (2 CH), 116.81 (CH), 118.57 (CH), 120.01 (2 CH), 121.68 (C), 122.00 (CH), 122.10 (CH), 126.81 (CH), 129.26 (2 CH), 129.49 (2 CH), 133.98 (C), 139.91 (C), 141.46 (C), 144.89 (C), 201.24 (C=O). MS (EI): m/z = 302 (100), 287 (12), 285 (10), 256 (10), 195 (47), 183 (16), 167 (54), 166 (22), 154 (14), 128 (13), 77 (18), 51 (9). Anal. Calcd (%) for C20H18N2O: C, 79.44; H, 6.00; N, 9.26. Found: C, 79.42; H, 5.99; N, 9.16. 19a Forke R, Krahl MP, Däbritz F, Jäger A, Knölker H.-J. Synlett 2008; 1870 19b Liégault B, Lee D, Huestis MP, Stuart DR, Fagnou K. J. Org. Chem. 2008; 73: 5022 19c Fuchsenberger M, Forke R, Knölker H.-J. Synlett 2011; 2056 19d Huet L, Forke R, Jäger A, Knölker H.-J. Synlett 2012; 23: 1230 20 6-Acetyl-5,11-dihydro-indolo[3,2-b]carbazole (10) Yellow solid; mp 244 °C. UV (MeOH): λ = 213 (sh), 223, 254, 306, 338 (sh), 357, 438 nm. Fluorescence (MeOH): λex = 223 nm, λem = 507 nm. IR (ATR): ν = 3456, 3400, 3051, 2920, 2851, 1640, 1605, 1558, 1512, 1457, 1418, 1353, 1320, 1292, 1270, 1221, 1186, 1168, 1144, 1109, 1010, 988, 961, 934, 866, 739, 692, 641, 621 cm–1. 1H NMR (600 MHz, CDCl3): δ = 2.96 (s, 3 H), 7.23–7.28 (m, 2 H), 7.46–7.49 (m, 3 H), 7.51–7.52 (m, 1 H), 8.10 (d, J = 7.8 Hz, 1 H), 8.17 (d, J = 8.1 Hz, 1 H), 8.22 (s, 1 H), 8.28 (br s, 1 H), 9.72 (br s, 1 H). 13C NMR and DEPT (150 MHz, CDCl3): δ = 30.93 (CH3), 106.42 (CH), 110.95 (CH), 111.00 (CH), 115.07 (C), 119.26 (CH), 119.46 (CH), 120.26 (C), 120.31 (CH), 121.90 (C), 122.37 (C), 124.08 (CH), 124.25 (C), 126.40 (CH), 126.73 (CH), 135.09 (C), 135.29 (C), 141.15 (2 C), 202.85 (C=O). MS (EI): m/z = 298 (100), 283 (30), 255 (64), 254 (10), 253 (11), 227 (11). 21 4-Acetyl-3-(phenylamino)carbazole (11) Yellow solid; mp 153 °C. UV (MeOH): λ = 204, 242, 306, 348 (sh), 452 nm. Fluorescence (MeOH): λex = 306 nm, λem = 411 nm. IR (ATR): ν = 3404, 2924, 2853, 1737, 1689, 1601, 1496, 1444, 1374, 1354, 1304, 1225, 1183, 1152, 1077, 1020, 903, 805, 748, 695 cm–1. 1H NMR (500 MHz, CDCl3): δ = 2.68 (s, 3 H), 6.26 (br s, 1 H), 6.85 (t, J = 7.4 Hz, 1 H), 6.90 (d, J = 8.3 Hz, 2 H), 7.18–7.23 (m, 3 H), 7.41–7.45 (m, 4 H), 7.86 (d, J = 8.0 Hz, 1 H), 8.19 (br s, 1 H). 13C NMR and DEPT (125 MHz, CDCl3): δ = 31.68 (CH3), 110.95 (CH), 113.05 (CH), 115.90 (2 CH), 119.37 (C), 119.78 (CH), 119.80 (CH), 121.55 (C), 122.19 (CH), 122.35 (CH), 126.30 (CH), 129.33 (2 CH), 129.49 (C), 131.49 (C), 136.22 (C), 140.18 (C), 145.58 (C), 205.90 (C=O). MS (EI): m/z = 300 (100), 285 (67), 284 (18), 257 (48), 256 (45), 255 (30). 22 Gensch T, Rönnefahrt M, Czerwonka R, Jäger A, Kataeva O, Bauer I, Knölker H.-J. Chem. Eur. J. 2012; 18: 770 23 Liebermann H. Ann. Chem. 1914; 404: 272 24a Knölker H.-J, O’Sullivan N. Tetrahedron 1994; 50: 10893 24b Knölker H.-J, Fröhner W, Reddy KR. Synthesis 2002; 557 24c Schmidt M, Knölker H.-J. Synlett 2009; 2421 25 Åkermark B, Eberson L, Jonsson E, Pettersson E. J. Org. Chem. 1975; 40: 1365 26a Börger C, Knölker H.-J. Synlett 2008; 1698 26b Börger C, Knölker H.-J. Tetrahedron 2012; 68: 6727 27 Wang W, Li T, Attardo G. J. Org. Chem. 1997; 62: 6598 28 Malasseziazole C (12-Formyl-5,11-dihydroindolo[3,2-b]carbazole-6-carboxylic Acid) (3) Brownish solid; mp >300 °C (decomp.). UV (MeOH): λ = 213, 247, 272 (sh), 307 (sh), 391, 465 nm. Fluorescence (MeOH): λex = 307 nm, λem = 455 nm. IR (ATR): ν = 3448, 3055, 2922, 2852, 1712, 1611, 1585, 1512, 1458, 1392, 1347, 1321, 1299, 1263, 1205, 1158, 1126, 1077, 1022, 954, 895, 839, 804, 741, 698, 653 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 7.22 (m, 2 H), 7.48 (t, J = 7.6 Hz, 1 H), 7.52 (t, J = 7.7 Hz, 1 H), 7.79 (d, J = 8.2 Hz, 1 H), 7.82 (d, J = 8.1 Hz, 1 H), 8.58 (d, J = 8.2 Hz, 1 H), 8.61 (d, J = 8.1 Hz, 1 H), 11.41 (s, 1 H), 11.44 (s, 1 H), 11.96 (s, 1 H), 13.72 (br s, 1 H). 1H NMR (600 MHz, CD3OD): δ = 7.11–7.13 (m, 1 H), 7.19–7.21 (m, 1 H), 7.40–7.45 (m, 2 H), 7.60 (d, J = 8.0 Hz, 1 H), 7.61 (d, J = 7.9 Hz, 1 H), 8.33 (d, J = 8.0 Hz, 1 H), 8.91 (d, J = 8.2 Hz, 1 H), 11.50 (br s, 1 H). 13C NMR and DEPT (125 MHz, DMSO-d 6): δ = 112.60 (CH), 112.72 (CH), 114.57 (C), 114.93 (C), 119.56 (CH), 119.77 (CH), 120.36 (C), 120.62 (C), 121.15 (C), 123.31 (C), 124.42 (CH), 125.09 (CH), 127.18 (CH), 127.51 (CH), 134.33 (C), 135.39 (C), 142.38 (C), 142.70 (C), 168.57 (C=O), 191.11 (CHO). ESI-MS (+25 V): m/z = 329.1 [M + H]+. 29 5,11-Dihydroindolo[3,2-b]carbazole-6,12-dicarboxylic Acid (17) Red solid; mp >294 °C (decomp.). UV (MeOH): λ = 211, 275 (sh), 294, 366 nm. Fluorescence (MeOH): λex = 294 nm, λem = 515 nm. IR (ATR): ν = 3448, 3413, 2920, 2850, 2577, 1642, 1610, 1570, 1543, 1501, 1473, 1457, 1429, 1314, 1297, 1229, 1207, 1151, 1112, 1021, 891, 857, 793, 763, 746, 699, 624 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 7.16 (m, 2 H), 7.45 (m, 2 H), 7.75 (d, J = 8.1 Hz, 2 H), 8.67 (d, J = 8.2 Hz, 2 H), 11.25 (s, 2 H), 13.95 (br s, 2 H). 13C NMR and DEPT (125 MHz, DMSO-d 6): δ = 110.44 (2 C), 111.63 (2 CH), 118.31 (2 CH), 120.35 (2 C), 120.63 (2 C), 124.28 (2 CH), 126.57 (2 CH), 134.72 (2 C), 141.81 (2 C), 168.47 (2 C=O). ESI-MS (+10 V): m/z = 345.2 [M + H]+. Supplementary Material Supplementary Material Supporting Information
